Regional differences in hippocampal excitability manifested by paired-pulse stimulation of genetically epileptic El mice.
Hippocampal excitability in El mice was studied by analyzing paired-pulse responses of population excitatory postsynaptic potentials (EPSPs) and population spikes (PSs). In vitro slice preparations from seizure-susceptible adult (15 weeks old) and non-seizure susceptible young (5 weeks old) El mice were compared with age-matched mother strain ddY mice. In CA1 area, paired-pulse inhibition of PSs was reduced by about 50% at 10 ms interpulse interval (IPI) in both 5 and 15 weeks old El mice when compared to ddY mice. Phenobarbital (200 microM) decreased paired-pulse ratio (PPR) by 30% in El mice, and bicuculline (1 microM) increased PPR by 80% in ddY mice at 10 ms IPI. These results suggest an intrinsic existence of decreased GABA(A) receptor-mediated inhibition in CA1 of El mice. In dentate gyrus (DG), an increase in paired-pulse facilitation of PSs was observed at intermediate IPIs (50-200 ms) in El mice at both ages, especially at 15 weeks of age, when 52%-increased PPR was recorded. The facilitation was not due to GABA(A) receptor-mediated inhibition and was not age-dependent. In CA3 area, increased paired-pulse facilitation of PSs and EPSPs over the range of 10-1000 ms IPIs was observed only in the 15-week-old El mice. The age-dependent appearance of seizure susceptibility was associated with the increase in excitatory synaptic transmission in CA3. Our results show that El mice possess excitatory/inhibitory synaptic transmission abnormalities in the hippocampus that could contribute to seizure predisposition.
Fueta
Y
Y
Department of Medical Technology, School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan. yukiko@med.uoeh-u.ac.jp
Kawano
H
H
Ono
T
T
Mita
T
T
Fukata
K
K
Ohno
K
K
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid